The long term goals of this research are to improve our understanding of the adaptations of the mechanisms of oxygen transport to conditions of prolonged oxygen deprivation. Prolonged hypoxia frequently occurs in cardiopulmonary disease, and is a feature of healthy individuals exposed to altitude. Prolonged hypoxia limits oxygen transport to and uptake by the tissues, particularly when oxygen demands are elevated, such as in exercise. Prolonged hypoxia is accompanied by changes in the oxygen transport system; understanding of the mechanisms of production of these changes, as well as of their functional relevance to oxygen transport, is limited. The low blood oxygen level plays a fundamental role in the limitation of the oxygen transport system in hypoxia; however, this is not the only factor. The proposed research will test the hypothesis that some of the cardiovascular changes that occur during acclimation to hypoxia limit oxygen delivery to the tissues. The research will be directed toward three interrelated specific aims: 1. To determine the functional role of the elevated hematocrit, independent of its effect on arterial oxygen concentration, on exercise capacity and oxygen transport to the tissues; 2. To investigate the mechanism of production and the functional significance of the systemic and pulmonary hemodynamic changes of prolonged hypoxia; these changes are characterized by decreased exercise cardiac output and elevated pulmonary and systemic vascular resistance; 3. To determine the mechanism of production and the functional significance of the changes in the distribution of blood flow during prolonged hypoxia. The experiments will be carried out in a rat model of adaptation to prolonged hypoxia. This model has been in use in our laboratory for several years; the characteristics of the oxygen transport system, as well as the respiratory, cardiovascular and acid-base responses to hypoxic exercise of this model have been described. This model allows for the characterization of several key variables that pertain to the systemic oxygen transport. The animals will be exercised in hypoxic and normoxic conditions, and their response to exercise will be compared with that of pair-fed littermates maintained in normoxia. These experiments will provide new information on the mechanisms of oxygen transport in prolonged hypoxia. This information should improve our understanding of the adaptation to prolonged oxygen deprivation and may help provide ways to improve this adaptation.